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Lian, F.* ; Xing, X.* ; Yuan, G.* ; Schäfer, C.* ; Rauser, S. ; Walch, A.K. ; Röcken, C.* ; Ebeling, M.* ; Wright, M.B.* ; Schmid, R.M.* ; Ebert, M.P.* ; Burgermeister, E.*

Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage.

Biochem. J. 438, 315-323 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile acids such as CDCA (chenodeoxycholic acid). FXR protects the liver and the intestinal tract against bile acid overload; however, a functional role for FXR in the stomach has not been described. We detected FXR expression in the normal human stomach and in GC (gastric cancer). FXR mRNA and protein were also present in the human GC cell lines MKN45 and SNU5, but not in the AGS cell line. Transfection of FXR into AGS cells protected against TNFα (tumour necrosis factor α)-induced cell damage. We identified K13 (keratin 13), an anti-apoptotic protein of desmosomes, as a novel CDCA-regulated FXR-target gene. FXR bound to a conserved regulatory element in the proximal human K13 promoter. Gastric expression of K13 mRNA was increased in an FXR-dependent manner by a chow diet enriched with 1% (w/w) CDCA and by indomethacin (35 mg/kg of body weight intraperitoneal) in C57BL/6 mice. FXR-deficient mice were more susceptible to indomethacin-induced gastric ulceration than their WT (wild-type) littermates. These results suggest that FXR increases the resistance of human and murine gastric epithelial cells to inflammation-mediated damage and may thus participate in the development of GC.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords bile acid; chenodeoxycholic acid (CDCA); farnesoid X receptor (FXR); keratin; gastric cancer; stomach
ISSN (print) / ISBN 0264-6021
e-ISSN 1470-8728
Journal Biochemical Journal / Reviews
Quellenangaben Volume: 438, Issue: 2, Pages: 315-323 Article Number: , Supplement: ,
Publisher Portland Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)